Human maturity onset diabetes, as well as the model system provided by the genetically diabetic mouse (db/db), is characterized by hyperglucagonemia accompanied by a lack of effective circulating insulin. Thus, the elucidation of the mode of glucagon action in regulation of carbohydrate metabolism is directly related to a better understanding of the causes of hyperglycemia in the diabetic state. Since one of the sites of glucagon action (by a yet unknown mechanism) occurs at the site of the metabolic interconversion of fructose-6-phosphate and fructose-1,6-bisphosphate, the present proposal plans to perform a comparative study of both phosphofructokinase and fructose-1,6-bisphosphatase isolated from the livers of genetically diabetic mice (db/db) and of their normal litter-mates. With this objective, the active (phosphorylated) and inactive (dephosphorylated) forms of liver phosphofructokinase will be separated from both the normal and the diabetic mouse. The kinetic and molecular properties of the isolated enzyme forms will be studied. Efforts will be made to isolate phosphofructokinase phosphatase and phosphofructokinase kinase in order to perform "in vitro" studies of the enzyme inter-conversion system. Fructose bisphosphatase will be isolated first from the livers of control mice. A search for a possible second form of the enzyme in the hyperglucagonemic state will be conducted by applying the developed purification procedure to the isolation of fructose bisphosphatase from the liver of the diabetic mouse. The kinetic and molecular properties of the isolated enzymes will be comparatively analyzed.